Induction of iNOS and formation of peroxynitrite in myocardial ischemia-reperfusion in rats

Patrick Y.K. Wong, Carl E. Hock, Robert Nagele, Peitan Liu

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Abstract

The role of nitric oxide (NO) in myocardial ischemia-reperfusion (MI/R) has been studied in rats. The left main coronary artery was ligated for 20 min, followed by reperfusion of 5 h by untying the ligature. MI/R induced myocardial tissue injury was indicated by the fact that there was a significant increase in arrhythmia score and marked decrease in creatine kinase activity of left ventricular free wall (LVFW) compared to sham control rats. Superoxide and nitric oxide formation in the I/R region of the heart were increased by 88% and 140%, respectively. Furthermore total and inducible nitric oxide synthase (iNOS) activities were elevated by 212% and 6.7-fold in the ischemic vs non-ischemic regions, respectively. iNOS accounted for 77% of the total NOS activity in the ischemic region. The induction of iNOS and formation of peroxynitrite, a reactive product of NO with Superoxide, were identified by immunohistodiemical staining with polyclonal anti-iNOS and monoclonal anti-nitrotyrosine antibodies, respectively. Sections of the ischemic area of the ventricular wall exhibited marked immunoreactivity with anti-iNOS and anti-nitrotyrosine antibodies, indicating the presence of iNOS and the formation of peroxynitrite. Similar staining results were found in lung tissue sections of MI/R rats. Our results indicate that the induction of iNOS and co-formation of peroxynitrite may play an essential role in MI/R tissue injury.

Original languageEnglish (US)
JournalFASEB Journal
Volume11
Issue number3
StatePublished - Dec 1 1997

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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